The development of effective vaccines for the prevention of human immunodeficiency virus (HIV) infection has been hampered by the lack of suitable in vivo HIV-1 infection animal models. Given the complex interaction of HIV with the immune system, there is no substitute for in vivo models for HIV infection and HIV vaccine evaluation. Existing animal models employed for HIV infection and vaccine development include chimpanzees infected with HIV-1, macaques infected with either SIV or HIV-2, cats infected with feline immunodeficiency virus and scid/scid mice reconstituted with human cells and infected with HIV. None of these models are ideal for the evaluation of HIV vaccines. The replication of HIV in chimpanzees is more restricted than in humans; therefore, vaccines shown to be protective in chimpanzees may fail to protect humans as chimpanzees may be more easy to protect from HIV infection. In addition, the number of chimpanzees available for research is small and therefore, it is difficult to obtain statistically significant experimental results, these animals are costly to maintain and once exposed to HIV these animals must be confined for the rest of their lives at a cost of greater than $100,000.00/chimp [Stott and Almond (1995) Nat. Med. 1:295]. While the supply of macaques is greater than that of chimpanzees, these animals are also costly to maintain. Most importantly, macaques cannot be infected with HIV-1 and thus, infection with HIV-2 or SIV must be used as a surrogate model for HIV-1 infection. Scid/scid mice reconstituted with human lymphocytes (hu-PBL-SCID mice), while permitting infection of the human cells with HIV-1, have failed to provide a model in which HIV vaccines and HIV immunity can be evaluated. This failure is due to the fact that most of the human T lymphocytes in the reconstituted scid/scid mice exhibit activated cell phenotypes soon after reconstitution, and almost all (&gt;99%) human T cells exhibit mature memory phenotypes in a state of reversible anergy [Rizza et al. (1996) J. Virol. 70:7958; Tarry-Lehmann and Saxon (1992) J. Exp. Med. 175:503; Tarry-Lehmann et al. (1995) Immunol. Today 16:529]. Therefore, the lack of sufficient numbers of immature naive T cells after reconstitution renders the hu-PBL-SCID model unsuitable for the evaluation of anti-HIV immunity following administration of a HIV vaccine.
The ultimate system for the study of HIV vaccines is, of course, the human. However, given the fact that HIV infection is almost invariably fatal in humans, ethical considerations limit the use of human volunteers in HIV vaccine evaluation. The art needs animal models in which anti-HIV immunity can be assessed to permit the evaluation of HIV vaccines.